The brain has a relatively high metabolic rate which requires a continual supply of glucose and oxygen via an intact cerebral circulation. Because of the delicate balance between energy supply and energy demand, the brain is especially vulnerable to a variety of insults. A hypothermia-induced reduction in the metabolic rate of the brain has been shown to decrease the pathological effects resulting from brain trauma. Energy metabolites and cyclic nucleotides have been measured in brains from 1) mice artificially rendered hypothermic and 2) hamsters that were allowed to hibernate. In the hypothermic state, the energy status of the tissue was preserved in both groups of animals. The concentrations of ATP and P-creatine were significantly higher than in brains from normothermic animals. During hibernation, the levels of GABA and lactate were elevated and those of cyclic GMP were nearly depleted. These changes were not observed in brains from hypothermic animals. The metabolic events which occur during hypothermia/hiberation may offer some clues on how to more effectively treat a number of pathological conditions of the brain.